In vivo tissue engineering devices, methods and regenerative and cellular medicine employing scaffolds made of absorbable material

ABSTRACT

Tissue engineering devices and methods employing scaffolds made of absorbable material for use in the human body for tissue genesis and regenerative and cellular medicine including breast reconstruction and cosmetic and aesthetic procedures and supplementing organ function in vivo.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/827,030, filed Mar. 23, 2020, which is a continuation-in-part of U.S.patent application Ser. No. 15/918,538, filed Mar. 12, 2018, now U.S.Pat. No. 10,595,986, each of which is incorporated herein by referencein its entirety.

BACKGROUND OF INVENTION Field of the Invention

The present invention relates to tissue engineering devices and methodsemploying scaffolds made of absorbable material implanted in the humanbody and use of such devices and methods in breast procedures, such asbreast reconstruction, augmentation, mastopexy and reduction, in variouscosmetic and aesthetic procedures involving tissue shaping andadipogenesis and in regenerative and cellular medicine to enhance andsupplement organ function in vivo.

Brief Discussion of Related Art

Breast implants are commonly used to replace breast tissue that has beenremoved due to cancer and are also commonly used for breastaugmentation. Most breast implants to replace the corpus mammae after amastectomy are either saline-filled or silicone gel-filled. Acellularmatrices are used mainly for lower pole breast coverage and the shapingof reconstructed breasts. These prior art breast implants have manydisadvantages and frequently cause tissue necrosis and capsularcontracture. Where the breast surgery is a partial mastectomy(frequently called a lumpectomy) implantable devices have been proposedfor placement in the surgical defect. One such device called the BioZorbimplant is marketed by Focal Therapeutics, Inc. and includes a rigidbioabsorbable body formed by framework elements producing anon-contiguous external perimeter, such as a coil. The result is thatthe device does not fill the surgical defect in many instances and,thus, does not achieve a consistently high quality aesthetic appearancewhich is the outcome desired following lumpectomy. Additionally, thedevice does not adequately stent the defect in smaller breasted, thinwomen and in such cases does not promote gradual healing of thelumpectomy space without scar contracture. U.S. Pat. Nos. 9,615,915 and9,980,809 to Lebovic et al and U.S. Pat. No. 10,413,381 to Hermann et alare representative of these implants which have the disadvantage of notproviding the cosmetic/aesthetic desired results but rather aredependent upon the size of the defect.

Autologous fat grafting is an increasingly common procedure in bothaesthetic and reconstructive surgery. Adipogenesis from the graftedautologous fat serves many purposes including, but not limited to,shaping and support of soft tissue, such as in the breast and thebuttocks (gluteus), and in in vivo tissue engineering.

In breast reconstruction and augmentation surgical procedures,autologous fat grafting is an extremely important step, and enhancedvascularization of the fat is important for improved fat survival.Autologous fat grafting for breast procedures typically involvesaspirating fat from the patient with a syringe and injecting theaspirated fat into the soft breast tissue. In the past, attempts toincrease vascular density of the injected fat have involved the use ofstructures to provide volume expansion to assist the fat grafting.Breast procedures and devices employing structures to providedistractive forces are exemplified by U.S. Pat. Nos. 8,066,691,9,028,526 and 9,974,644 to Khouri and U.S. Patent ApplicationPublication No. 2008/03006812 to Rigotti et al and are also described inan article entitled “Megavolume Autologous Fat Transfer: Part I. Theoryand Principles” authored by Khouri et al, PRS Journal, Volume 133,Number 3, March 2014, pages 550-557. The prior art attempts to improvefat survival have not been successful from a practical standpoint andhave had many disadvantages, primarily the need to remove the structuresafter the surgical procedure.

Many efforts have been made in medicine to replace pharmaceuticals withcellular therapies and to use tissue engineering and regenerativemedicine to replace synthetic replacement parts. Science has attemptedin the past to engineer replacement parts and organs for the human body.Most efforts have focused on the use of stem cells and decellularizedallograft organs. Unfortunately, these attempts and associated therapieshave not succeeded in clinical practice, largely due to the problem ofdeveloping vascular supply to the large volumes of tissue required forthese therapies. Prior art attempts to accomplish in vivo tissueengineering have failed to take advantage of the self-organizingproperties of healing tissues. Under the influence of macrophage type-2inflammation, healing tissues under the influence of proteins, likecytokines and extra cellular matrix proteins, have the ability toorganize themselves into biologically authentic order and structure.This activity requires physical support and a blood supply, on a fractalorder, and the prior art has failed to provide these requirements.

In the past, attempts have been made to use tissue engineeringtechniques to combine stem cells and exomes employing scaffolds toovercome the problem of donor tissue scarcity. The attempts have notbeneficially affected the function (parenchyma) of the organ due to theinability to integrate fully functioning vascular architectures into theengineered construct. Thus, there has been a need for tissue engineeringdevices for use in organ generation and/or supplementing the function oforgans in the human body.

SUMMARY OF THE INVENTION

Absorbable” material means a material that is degraded in the body. Itis noted that the terms “absorbable”, “resorbable”, and “degradable” areused in the literature interchangeably with or without the prefix “bio”.Accordingly, absorbable material as used herein means a material brokendown and gradually absorbed, excreted or eliminated by the body whetherthe degradation is due to hydrolysis or metabolic processes. A preferredlong term absorbable material for use with the present invention isPoly-4-Hydroxybutyrate, which is commonly referred to as P4HB, and ismanufactured by Tepha, Inc., Lexington, Mass. P4HB is typicallyavailable in sheets which are referred to as two-dimensional materialsand is also available as three-dimensional materials which can be shapedby molding. Absorbable materials useful to make the scaffold of thetissue engineering device according to the present invention arefrequently referred to as biodegradable polymers such as the following:polylactic acid, polygllycolic acid and copolymers and mixtures thereofsuch as poly(L-lactide) (PLLA), poly(D,L-lactide) (PLA), polyglycolicacid or polyglycolide (PGA), poly(L-lactide-co-D,L-lactide) (PLLA/PLA),poly(L-lactide-co-glycolide) (PLLA/PGA), poly(D,L-lactide-co-glycolide)(PLA/PGA), poly(glycolide-co-trimethylene carbonate) (PGA/PTMC),poly(D,L-lactide-co-caprolactone) (PLA/PCL) andpoly(glycolide-co-caprolactone) (PGA/PCL); polyhydroxyalkanoates,poly(oxa) esters, polyethylene oxide (PEO), polydioxanone (PDS),polypropylene fumarate, poly(ethyl glutamate-co-glutamic acid),poly(tert-butyloxy-carbonylmethyl glutamate), polycaprolactone (PCL),polycaprolactone co-butylacrylate, polyhydroxybutyrate (PH BT) andcopolymers of polyhydroxybutyrate, poly(phosp-hazene), poly(phosphateester), poly(amino acid), polydepsipeptides, maleic anhydridecopolymers, polyiminocarbonates, poly[(97.5% dimethyl-trimethylenecarbonate)-co-(s.5% trimethylene carbonate)],poly(orthoesters)tyrosine-derived, polyaryates, tyrosine-derivedpolycarbonates, tyrosine-derived polyiminocarbonates, tyrosine-derivedpolyphosphonates, polyethylene oxide, polyethylene glycol (PEG),polyalkylene oxides (PAO), hydroxypropylmethyl-cellulose,polysaccharides such as hyaluronic acid, chitosan and regeneratecellulose, and proteins such as gelatin and collagen, and mixtures andcopolymers thereof, among others as well as PEG derivatives or blends ofany of the foregoing. Desirably, polymeric materials can be selected forthese systems and methods that have good strength retention, such aspolydioxanone, silk-based polymers and copolymers,poly4-hydroxybutyrates, and the like.

The present invention overcomes the disadvantages of the prior art byconfiguring a scaffold made of porous absorbable material to providephysical support for a large volume of tissue, including autologous fat,in a plurality of tissue engineering chambers arranged around a corewhich can be hollow to accommodate blood vessels. In one embodiment, thetissue engineering device of the present invention employs a scaffoldmade of a mesh absorbable material formed of a mono-filament polymerknitted mesh which provides a biologic scaffold matrix for cellattachment and protein organization. The matrix is invaded bycapillaries, in a granulation type process that transforms the mesh intoengineered fascia. The absorbable mesh material structure has aplurality of partially open tissue engineering chambers. The chamberscan be formed by folds in one or more sheets of absorbable material andarranged radially around a central core. The chambers can be segmentedand/sub-segmented to increase the surface area of the scaffold. Thetissue engineering device of the present invention has a shape to beimplanted in an anatomical space in fascia of the human body, and thetissue engineering chambers have an aggregate surface area greater thanthe fascia surface area in the anatomical space. The anatomical spacecan be a defect created during surgery in superficial fascia, forexample in the breast, or in deep fascia adjacent an organ, for examplethe pancreas, kidneys or liver, when the tissue engineering device isemployed for recellularization with functional parenchymal cells. Withrespect to the pancreas, the tissue engineering device of the presentinvention can be used to replace insulin-producing islet beta cellsdestroyed in some types of diabetes. With respect to the liver, thetissue engineering device of the present invention can be used toproduce a plentiful source of hepatocytes for regenerating liver tissueand treating metabolic diseases.

In another embodiment of the present invention, the scaffold has an openor hollow core designed for receiving a vascular pedicle having anappropriately sized artery with its vena comitans, fascia and associatedfat such that a large volume of engineered tissue is broken down intofractal units of tissue with its own circulation. The radial arrangementof tissue engineering chambers, which can be formed of segments andassociated sub-segments, surround the core and break down the largevolume of tissue into units approximately 5 cc in volume, which is thevolume whereby self-organizing tissues sprout at the terminus ofcapillary growth. The engineering of large volumes of vascularizedliving tissue is accomplished with the present invention by acombination of man-made and designed structures and in vivo biologiccells and proteins that organize themselves into healthy tissues.

The tissue engineering devices and methods according to the presentinvention can be utilized in the body to encourage rapid tissue ingrowthfor various reconstructive and cosmetic procedures relating to tissuegrafting, particularly, autologous fat in soft tissue areas including,but not limited to, the breast and the buttocks. In the past, autologousfat grafting has involved aspirating fat from a patient with a syringeand injecting the aspirated fat into the soft tissue. As noted above,many prior art procedures and/or devices utilized for fat graftinginvolve application of distractive forces whereas the tissue engineeringdevices and methods of the present invention obviate the need for suchdistractive forces by employing scaffolds having tissue engineeringchambers radially arranged around a central core to collect andvascularize tissue.

The tissue engineering devices and methods of the present inventionemploy a scaffold made of absorbable material. In one embodiment, thepresent invention employs an open-pore knit pattern of absorbablematerial to encourage rapid tissue ingrowth through the micro-pores ofthe scaffold.

The scaffold employed in the tissue engineering device of the presentinvention permits lipoaspirate fatty tissue injected in the tissueengineering chambers to be mixed with the absorbable material thusholding the micro-globules of liposuctioned fat in place in athree-dimensional, scattered fashion to promote vascularization andprevent pooling of the fat which otherwise could lead to necrosis.Additionally, the tissue engineering chambers can be, prior to insertionin the body, coated with substances known to encourage tissueregeneration and then coated with selected tissue cells such aspancreatic islet cells, hepatic cells, or other cells as well as withstem cells and exosomes genetically altered to contain genes fortreatment of patient illnesses. The radially arranged tissue engineeringchambers provide good neovascularization with mononuclear inflammatorycells and multi-nucleic giant cells as well as adipogenesis on theabsorbable material surfaces, in the absorbable material and between thelayers of folded absorbable material.

The number of tissue engineering chambers can vary but are normallysomewhere between eight and ten thus dividing the greater overall volumeof the space for tissue expansion into smaller, subunit spaces. Thejoining together of the tissue engineering chambers around a centralcore adds to the stability of the scaffold while minimizing the requiredmesh absorbable material.

The scaffold of the tissue engineering device of the present inventionhas multiple points of connection to form a tension system, and fattytissue is created which will eventually fill the tissue engineeringchambers to create a structure that will bend but not break and returnto its original equilibrium shape after distorting influences areremoved. Advantageously, the absorbable material is a mesh materialcomposed of a loose-knit monofilament, such as an absorbable polyesterlike Poly-4 Hydroxybutyrate (P4HB) which is a naturally occurringpolymer known to have antibacterial properties and induces M2 phase ofinflammation leading to tissue regeneration.

Globules of fat and partial globules broken apart by surgical dissectionwill fall into the tissue engineering chambers which is desirable sincethe collagen matrix of the fascia system with its capillaries andarterioles are known to be the location of new adipose tissue creationor adipogenic sites. The large surface area of the scaffold providesstructure for neovascularization and three-dimensional locations fordistribution of priming substances such as liposuction aspirant. Inother priming maneuvers, loose knit, microporous material of thescaffold can be coated with proteins known to promote tissueregeneration and can be covered with other chemical compounds. Thescaffold can be colonized with undifferentiated stem cell transplantsfrom healthy cells that grow and produce metabolic compounds.

The tissue engineering device scaffolds of the present invention can befabricated using a wide range of polymer processing techniques. Methodsof fabricating the tissue engineering scaffolds include solvent casting,melt processing, fiber processing/spinning/weaving, or other means offiber forming extrusion, injection and compression molding, lamination,and solvent leaching/solvent casting. One method of fabricating tissueengineering absorbable material scaffolds involves using an extrudersuch as a Brabender extruder to make extruded tubes.

Another fabrication method involves preparing a nonwoven absorbablematerial scaffold from fibers produced from the melt or solution andprocessed into woven or nonwoven sheets. The properties of the sheetscan be tailored by varying, for example, the absorbable material, thefiber dimensions, fiber density, material thickness, fiber orientationand method of fiber processing. The sheets can be further processed andformed into hollow tubes.

Another method involves melt or solvent processing a suitable absorbablematerial into an appropriate mold and perforating the material using alaser or other means to achieve the desired porosity. Other methodsinclude rolling a compression molded absorbable material sheet into aloop and heat sealing. The tissue engineering devices of the presentinvention can be seeded with cells prior to implantation or afterimplantation.

The tissue engineering devices and methods of the present invention canbe used for in vivo tissue engineering for organs, including thekidneys, pancreas and liver. The absorbable material is a mesh to allowinvasion of fibroblasts to produce collagen which wraps around themonofilament fibers of the mesh. Capillaries grow into the mesh bringingcirculation to a large three-dimensional space in the mesh engineeredfascia. Lipoaspirate is added to self-organize into a stroma in thespaces between the mesh, the stroma being the supportive tissue of theorgan consisting of connective tissues and blood vessels. Another addedingredient is stem cells and exosomes which are seeded on the scaffoldwhen it is implanted. The type of stem cell and/or exosome is chosendepending on the function of the organ being engineered. For example,stem cells from adipose tissue or mesenchymal stem cells are appropriatefor breast reconstruction. Glomerular stem cells are used forengineering a kidney. Stem cells associated with pancreatic islet cellsare used for the pancreas to treat diabetes. The stem cells develop theparenchyma of the organ.

Accordingly, it can be seen that the tissue engineering device of thepresent invention presents a building block for in vivo organdevelopment (engineering) or supplementation in that the tissueengineering device provides mesh to engineer a supportive fascia whichbrings vascularity to a large three-dimensional space and stromal cellsthat are the supportive filler and functional cells of a specific organin the parenchyma.

Along with the above noted advantages of the present invention in tissueengineering, the present invention has the additional advantages ofbeing used as, essentially, a bio-hybrid organ for hormone replacementtherapy to obviate the need for hormone pellets. That is, instead ofimplanting slowly dissolving pellets to release a set amount of estrogenor testosterone, the tissue engineering device of the present inventioncan be used to colonize cells that are a part of human body circulationto release the hormones naturally which is particularly advantageous inpatients whose increased age has reduced their hormone levels.Similarly, the tissue engineering device of the present invention can beimplanted in individuals with hypothyroidism to be the locus for acolony of transplanted cells that produce thyroid hormone. When thetissue engineering device of the present invention is used as abio-hybrid organ, endocrine cells are generated with the individual'shypothalamus and pituitary glands controlling the amount of hormoneproduction in accordance with their normal function. A pancreaticbio-hybrid tissue engineering device according to the present inventioncan also allow an islet cell colony to evade attack by the immune systemin individuals with Type 1 diabetes. CRISPR technology can be used totake autologous islet cells and disable their NLRC5 gene, and the isletcells can then be implanted in the tissue engineering device allowingthe device to function as a bio-hybrid endocrine organ without beingattacked by the immune system. Tissue engineering devices of the presentinvention implanted in the breast do not present the complications ofcapsular contracture and infection frequently associated with siliconeimplants used for breast reconstruction in that adipogenesis is enhancedby capillaries from the superficial fascia growing into the open, poroussurfaces of the scaffold which have received the small globules ofaspirated fat. Thus, healthy tissue with good vascularity is created toavoid infection. When the tissue engineering device of the presentinvention is implanted following lumpectomy, the spherical-type shapefills the defect and promotes gradual healing of the lumpectomy spacewithout scar contracture while the scaffold acts as a stent preventingwound contracture and scarring and promoting M2 regenerative healing ofthe lumpectomy defect. The round surface of the spherical-like scaffoldminimizes damage to delicate tissue, prevents extrusion and, morecompletely, approximates the lumpectomy defect than prior art devices.

Other aspects and advantages of the tissue engineering devices andtissue engineering methods of the present invention will become apparentfrom the following description of the invention taken in conjunctionwith the accompanying drawings wherein like parts in each of the severalfigures are identified by the same reference characters.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an embodiment of the in vivo tissueengineering device of the present invention.

FIG. 2 is a top view of the tissue engineering device of FIG. 1.

FIG. 3 is a broken perspective view illustrating a method of fabricationof the tissue engineering device of the present invention.

FIG. 4 is a broken perspective view illustrating implant of a tissueengineering device of the present invention.

FIG. 5 is a broken perspective view illustrating implant of a tissueengineering device of the present invention in the breast aftermastectomy.

FIGS. 6 and 7 are top perspective and bottom plan views, respectively,of a tissue engineering device of the present invention modified toinclude a layer of absorbable material on a disc-like distal end surfaceand detachable tubing on a disc-like proximal end surface.

FIG. 8 is a perspective view of a tissue engineering device of thepresent invention with short term absorbable material in the tissueengineering chambers.

FIGS. 9 and 10 are broken perspective views of a tissue engineeringdevice of the present invention used for supplementing kidney function.

FIGS. 11 and 12 are side views of tissue engineering devices of thepresent invention having varying profiles.

FIG. 13 is a side view of a tissue engineering device of the presentinvention having a tubular configuration.

FIG. 14 is a side view of a tissue engineering device of the presentinvention having a spherical-like configuration for implant after alumpectomy.

DETAILED DESCRIPTION OF THE INVENTION

An in vivo tissue engineering device 20 according to the presentinvention is shown in FIGS. 1 and 2 and includes a scaffold 22 made ofone or more sheets of mesh absorbable material which is, by nature,porous. The scaffold has a wide base or proximal portion 24, a narrowerapex or distal portion 26 and a tapering, sidewall 28 extending betweenthe base portion and the apex portion. The sidewall 28 is formed by aplurality of partially open, tissue engineering chambers 30 such thatthe sidewall has a rugose configuration formed by pleats or folds of theone or more sheets of absorbable material. The scaffold has a hollowinner region 29 which can be formed by a central core 32 extendingbetween the base portion and the apex portion. If required by size,volume and stability, a plurality of L-shaped tubular struts 34 made ofabsorbable material can be radially arranged on the scaffold with legsextending through the core and bent 90° to terminate adjacent theperimeter of the base portion. As shown, the scaffold has a truncatedgeometrical shape designed to be placed in the body in a position wherethe base portion is adjacent bodily tissue to define a fixation oranchoring location where the scaffold is supported and the apex portionis spaced from the fixation location. When the tissue engineering deviceis used for breast procedures, such as breast reconstruction oraugmentation (e.g. after mastectomy, implant replacement, mastopexy andother breast procedures), the scaffold can have a truncated shapesimilar to a brassiere cup such that the shape of the scaffold can beconsidered to be a frustoconical-like or pyramidal-likethree-dimensional structure.

The scaffold can be made of one or more pleated sheets of meshabsorbable material or can be molded of porous absorbable material to beunitary in nature as described above. A segment 36 of the absorbablematerial forming the side wall 28 is shown in FIG. 3. The pleated sheetsof absorbable material are folded as shown at the bottom 38 to form thetissue engineering chambers 30, each of which is defined by opposingpanels 39 extending from the bottom to form interior walls. Adjacentsheets or panels of absorbable material can be fixed or connected asshown at 40 to form sub-segment tissue engineering chambers 30′ and 30″.If the scaffold is not molded or otherwise unitarily formed, theconnection shown at 40 can be achieved by welding to attach all pointsof contact in the structure. The connection of adjacent tissueengineering chambers creates a contiguous outer surface for the scaffoldand stabilizes the compression and tensioning forces exerted on thescaffold by bodily tissue to achieve a floating equilibrium ortensegrity via the non-rigid tissue engineering chambers. Once fat hasgrown into the tissue engineering chambers, the fat will cooperate withthe structure of the scaffold to create biotensegrity. The struts 34 areused if extra support is required due to the weight of tissue in thescaffold, and preferably the struts should terminate below the endsurface of the distal portion and not extend beyond the perimeter of thedisc surface of the proximal portion. Additional tissue engineeringchambers 30V are formed in the spaces between panels 39 of adjacenttissue engineering chambers. Accordingly, the aggregate surface area ofthe mesh absorbable material provided by the tissue engineering chamberswill be substantially greater than the fascia surface area in theanatomical space in which the tissue engineering device is implanted ascan be seen in FIGS. 4 and 5. As noted above, the tissue engineeringchambers 30 are formed or divided into sub-segments 30′ and 30″, and thesub-segments increase the stability of shape of the scaffold, due totensegrity, and support the over-all volume of adipose tissueengineering required to perform breast reconstruction. The tissueengineering chambers each, desirably, generates an average of 5 cc ofadipogenesis such that a scaffold having fifty tissue engineeringchambers allows the transplant of 250 cc with no fat necrosis. In thescaffold employed in the tissue engineering device embodiment of FIG. 1,the chambers 30 would hold 7 ccs of fat, the chambers/sub-segments 30′would hold 5 ccs of fat and the chambers/sub-segments 30″ would hold 3ccs of fat. The number of tissue engineering chambers/sub-segmentsdepends on the stability provided by the L-shaped struts and the amountof absorbable material desired. The tissue engineeringchambers/sub-segments are each arranged in a ring such that the scaffoldis formed of a plurality of rings of tissue engineering chambers to formvarious geometric configurations for the scaffold. Looking at FIG. 2,tissue engineering chambers 30 form an outer ring, tissue engineeringchambers 30′ form an intermediate ring and tissue engineering chambers30″ form an inner ring. For example, the plurality of rings can bearranged in tiers having decreasing diameters such that the sidewall 28is tapered and the scaffold has a frustoconical-like configuration.Where the plurality of rings has substantially the same diameter, thescaffold will have a tubular/cylindrical configuration as shown in FIG.13. Hemispherical-like and spherical-like configurations can be achievedby varying the diameter of the rings. A spherical-like configuration canalso be achieved by securing two hemispherical-like scaffolds togetheras shown in FIG. 14. The proximal portion 24 of the scaffold has adisc-like end surface 42 and the distal portion 26 of the scaffold has adisc-like end surface 44, both end surfaces being made of absorbablematerial. In the truncated geometrical shape shown in FIG. 1, the endsurfaces 42 and 44 are disposed at the base and apex, respectively, ofthe scaffold and have openings 46 and 48 therein, respectively, alignedwith hollow central core 32.

A tissue engineering method according to the present invention will bedescribed in connection with a breast procedure after mastectomy andwith reference to FIGS. 4 and 5. It is important that the anatomicalspace in fascia, i.e. the mastectomy defect, be stented and held open toprevent scar contracture of the wound which is prohibitive to fatregeneration, i.e. adipogenesis. In order for adipogenesis to takeplace, a low tissue tension is required, and a nearby capillary bloodsupply is needed. The tissue engineering method comprises the steps ofimplanting scaffold 22 in the anatomical space in the fascia 50 createdduring the mastectomy, anchoring the proximal portion of the scaffold inthe space 50 with the proximal end disc-like surface abutting thefascia, inserting autologous tissue, normally autologous liposuctionedfat, in the tissue engineering chambers 30, pulling a vascular flappedicle 52 along with the blood vessels (perforator 54 shown in FIG. 4)into the hollow inner region 29 of the scaffold formed by the hollowcore 32 and positioning the vascular flap pedicle in the distal portionof the scaffold to position the blood vessels 54 along the hollow innerregion to provide capillary blood supply to the autologous tissue in thetissue engineering chambers 30. For breast procedures, the vascular flappedicle is dissected from a small pectoral muscle island flap having aperforator coming from the thoracoacromial artery, and theperforator/vascular flap pedicle is accessed by instruments passedthrough the opening 48 in the disc-like end surface 44 of the distalportion 26. A forceps 56 is shown grasping a suture 58 tied around thevascular flap pedicle. Accordingly, blood vessels can be pulled by thesuture through the central hollow core from the base up through the apexat the time of implant of the scaffold and the suture can be tied to theapex of the scaffold to anchor the vascular flap pedicle in place beforethe scaffold is sutured to surrounding fascia in the anatomical space 50to prevent rotation or displacement of the scaffold in the anatomicalspace. The autologous tissue inserting step can be performed prior toimplant of the scaffold, after implanting of the scaffold or prior toand after implant of the scaffold. The tissue engineering method can beenhanced by creating negative pressure in the scaffold and by fillingthe tissue engineering chambers with loose felt cellulose matrix priorto inserting fat.

FIG. 5 shows a scaffold 22 according to the present invention implantedin a space 50 after mastectomy within a breast with the scaffold havingfewer tissue engineering chambers 30 than the scaffold shown in FIGS. 1and 4 and illustrates cannulas 62 for injecting microglobules of thefat, approximately 1 to 1.5 mm in diameter, between the skin envelopeand the scaffold 22, under the scaffold and near the chest wall and intothe tissue engineering chambers 30 and 30′. Granulation tissue, acollagen and extra cellular protein matrix created by fibroblasts mixedwith rich capillary growth emanating from the pectoral muscle vascularflap/perforator 52 in the hollow core 32 of the scaffold, is generatedin the center of the scaffold to create centrally located supportivevascular tissue which is mimicked by tissue growing in from theperipheral surfaces and from the surrounding superficial fascia remnantsfrom the mastectomy dissection. Accordingly, the surfaces of the meshabsorbable material, which is segmented to form the tissue engineeringchambers, have vascular supported tissue ingrowth from the outside inand from the inside out producing a large vascularized absorbable meshscaffold that can sustain adipogenesis. The termination of the struts 34to not extend beyond the perimeter of the base of the scaffold is shownat 64.

FIGS. 6, 7 and 8 show modifications of the tissue engineering device 20shown in FIG. 1. FIG. 6 shows a layer of cellulose matrix 66, such asmethyl cellulose, disposed on the distal end disc-like surface 44 havinga thickness of approximately 1 cm. Fat is injected in the layer, and thelayer acts as a separation of the areolar dermis from the scaffold tofacilitate lifting the skin envelope and nipple areolar dermis away fromthe scaffold during subsequent fat grafting, if required. FIG. 7 showstubing 68 with holes therein detachably carried on the proximal portiondisc-like end surface 42 communicating with a small suction pump 70 tocreate negative pressure in the scaffold and to drain excess fluid. Thetubing 68 is also shown in FIG. 6.

FIG. 8 shows the application of a loose felt of cellulose matrix 72,such as methyl cellulose, to the mesh absorbable material forming thetissue engineering chambers 30, 30′ and 30″ of the scaffold. The loosefelt greatly increases the surface area of the mesh absorbent materialbut will dissolve much faster since the absorbable material used tofabricate the scaffold is considered to be a long term absorbablematerial relative to the cellulose matrix which is considered to be ashort term absorbable material. The cellulose fibers of the cellulosematrix will additionally hold fat globules in place and also act as anadditional surface for capillary ingrowth.

A modification of the tissue engineering device of FIG. 1 to provide akidney-type function is shown in FIGS. 9 and 10 with parts labeled toexplain their function. The scaffold 22 has essentially the samestructure as the scaffold shown in FIG. 5 with the addition ofmicrotubules in semipermeable membranes disposed in the chambers 30dividing the chambers in half. In FIG. 9, a tube communicates with thehollow central core at the opening 48 in the disc-like end surface ofthe distal portion of the scaffold for exit of urea to permit drainageto the bladder. In FIG. 10, urea exits from the proximal portion of thescaffold.

Embodiments of scaffolds 22 for use in the tissue engineering device ofthe present invention are shown in FIGS. 11 and 12 where the tissueengineering chambers 30 are not formed with sub-segments. The interiorhollow core 32 and the L-struts 34 are covered by rugose draping sheetsof mesh absorbable material. The embodiment shown in FIG. 11 has a basewider than its height and would be covered with liposuctioned fatwhereas the embodiment shown in FIG. 12 has a height greater than thewidth of its base and would be implanted behind the breast gland (corpusmammae) to effect increased projection of the breast. These embodimentscan be used in instances of breast reduction and mastopexy afterimplantation. The patient's cells, including fibroblast producingcollagen and capillaries grow into the scaffold and create an engineeredfascia-like tissue which persists after the mesh fibers are absorbed.

The embodiment of the scaffold 22 shown in FIG. 13 is tubular andessentially cylindrical and would be employed in tissue engineeringdevices used with filter-type organs. The hollow central core 32 runsthe length of the cylindrical scaffold. When used for the kidneys,two-dimensional circular discs, which are the semipermeable membranescontaining the microtubule collecting ducts, are spread out along thelongitudinal axis of the scaffold at regular intervals. Flanked oneither side of each semipermeable membrane are the absorbable materialchambers/segments 30 where the engineered adipose tissue grows. Theadipose tissue gets blood supply by the vascular flap pedicle (in thecase of use with the kidneys, the inferior epigastic artery) which isdissected out of the muscle in the lower abdomen, then pulled throughthe central core. The drainage tube shown in FIGS. 9 and 10 collectsurine and runs from the distal to proximal ends, where it is thentunneled to the bladder like a ureter.

A spherical-type scaffold 22 is illustrated in FIG. 14 and would be of asize smaller than scaffolds used for total breast reconstructionfollowing mastectomy. The embodiment of FIG. 14 is designed for use toreconstruct partial mastectomies, otherwise known as lumpectomies. Thediameter of the spherical-type scaffold would normally be between 2.5 cmand 5 cm, and the central hollow core 32 would normally have a diameterof approximately 1 cm and facilitates tissue ingrowth and expeditesabsorption. The spherical-type scaffold for use after a lumpectomy wouldnot require any fat grafting or use of vascular perforator pedicles dueto the large ratio of surface area to volume which insures rapidingrowth of tissue. The spherical-type scaffold will hold apartremaining tissue that surrounds a lumpectomy defect and prevent collapseand scarring. The negative pressure of the anatomical lumpectomy spaceinduces tissue ingrowth and adipogenesis in the same manner as thetissue engineering chambers previously described without the need forfat grafting. A fractal version of the spherical-type scaffold can be onthe order of 1 to 1.5 mm to permit injection as filler into existingsuperficial fascia and would be replaced by tissue and fat fromadipogenesis without the need for liposuction and fat grafting. In orderto achieve a desired aesthetic outcome following lumpectomy, the smallspherical-type scaffold is implanted and fills the defect to promotegradual healing of the lumpectomy space without scar contracture. Thespherical-type scaffold acts as a stent against wound contracture andscarring and promotes M2 regenerative healing of the lumpectomy defect.The spherical-type scaffold includes a plurality of tissue engineeringchambers connected with one another as previously described to present acontiguous periphery to fill the defect. Titanium micro-clips can bemounted to the surface of the spherical-type scaffold to define itslocation for post-lumpectomy breast procedures and mammograms. Due tothe small size of the spherical-type scaffold, which will have adiameter between 2.5 and 5 cm, the scaffold will typically have only 12segments with only 24 subsegments. Each subsegment will have anapproximately 5 cc volume.

The tissue engineering device of the present invention can be implantedin various locations of the body particularly in anatomical spaces inthe fascia, both in the superficial fascia and the deep fascia. Thescaffold of the tissue engineering device can have any shape or sizedependent upon the anatomical space in fascia and the functionalrequirements of the scaffold (for example, for breast reconstructionafter mastectomy, for cosmetic or aesthetic purposes relating to thebreast or other soft tissue, such as the buttocks, or for variousfunctional organs of the body). Accordingly, the scaffold would besmaller in size and essentially spherical in shape for lumpectomies. Thescaffold can be placed in a space in the body created by surgicaldissection to divide the space into segments and sub-segments. Thesurfaces of the scaffold invite tissue ingrowth consisting offibroblasts making collagen fibers which surround the polymer filamentsof the absorbable material and capillary vascular ingrowth. The spacesbetween the pleats/chambers leave room for new adipose tissue creation,through a process mediated by mechanical signals, due to low tissuetension created by holding the surgical dissection apart with thescaffold. This stimulates stromal cells in the fascia to secrete protein“cytokines” such as CXCL12 which attracts stem cells from circulation tomigrate and congregate in the space occupied by the tissue engineeringdevice. As a result, a healthy, well vascularized engineered tissueresults in the location of implantation of the tissue engineeringdevice. The absorbable material scaffold can be covered with variouschemical compounds, cells, and proteins prior to implantation, dependingon various regenerative therapeutic goals. The tissue engineering devicethus becomes an in vivo bioreactor acting as a repository forgenetically repaired, autologous patient cells, or allograft donorcells, that have been genetically altered or repaired, e.g. for example,with CRISPR technology. Once cells have been genetically modified invitro, the cells are transplanted into the tissue engineering devicebioreactor environment, where the cells find an incubator environmentfor growth and are exposed to a rich circulation which can send theproducts of the repaired cell line into the patient's blood stream. Oneexample is the treatment of diabetes. Type I diabetics have aninadequate number of functioning pancreatic islet cells, which makeinsulin. The beta cells of the pancreatic islets secrete insulin andplay a significant role in diabetes. Repaired autologous beta cells orallograft beta cells can be transplanted into the tissue engineeringdevice for the treatment of diabetes. The tissue engineering device canbe placed anywhere within the fascia system of the body, but mostconveniently at locations such as the lower lateral abdominal region,posterior hip region above the buttocks, or the upper chest, just belowthe clavicle. These locations allow implantation via outpatient minorsurgical procedures, using local anesthesia and mild sedation.

The porosity of the porous absorbable material from which the scaffoldis made will be determined based on its area of use in the body.Porosity is important to the reaction of the tissue to the scaffold.Macroporous mesh absorbable materials that have large pores facilitateentry of microphages, fibroblast and collagen fibers that constitute newconnective tissue. Microporous mesh absorbable materials, with poresless than 10 micrometers, have shown a higher rejection rate due to scartissue rapidly bridging the small pores. Though there is no formalclassification system for pore size, in most instances the scaffold willbe made of a macroporous mesh absorbable material with pores greaterthan 10 micrometers.

Inasmuch as the present invention is subject to many variations,modifications and changes in detail, it is intended that all subjectmatter discussed above or shown in the accompanying drawings beinterpreted as illustrative only and not be taken in a limiting sense.

What is claimed is:
 1. An implantable prosthesis comprising: athree-dimensional, tissue infiltratable body of biocompatible materialhaving a proximal end and a distal end spaced from the proximal end, thebody including: a core extending along a core axis from the proximal endto the distal end; a plurality of body segments arrangedcircumferentially about the core, each of the plurality of scaffoldsegments extending in an outward radial direction away from the coreaxis, each body segment including at least two scaffold panelsfabricated from a sheet of the biocompatible material, the sheet beingfolded about a first fold oriented in the outward radial direction toform the body panels; and a plurality of chambers formed by theplurality of scaffold segments, the plurality of chambers arranged toface in the outward radial direction away from the core.
 2. Theimplantable prosthesis according to claim 1, wherein each of theplurality of chambers extends along a corresponding chamber axis whichis transverse to the core axis.
 3. The implantable prosthesis accordingto claim 2, wherein each chamber axis extends in a different radialdirection relative to each other.
 4. The implantable prosthesisaccording to claim 3, wherein the chamber axis of each of the pluralityof chambers is oriented at an angle relative to the proximal end, theangle of the chamber axis being the same for each chamber in a firstgroup of chambers.
 5. The implantable prosthesis according to claim 2,wherein each of the plurality of chambers is open in the correspondingoutward radial direction.
 6. The implantable prosthesis according toclaim 1, wherein each of the plurality of chambers has a size whichincreases in the outward radial direction.
 7. The implantable prosthesisaccording to claim 6, wherein each of the plurality of chambers has awidth which increases in the outward radial direction.
 8. Theimplantable prosthesis according to claim 1, wherein the body has afrusto-conical shape.
 9. The implantable prosthesis according to claim1, wherein the body has a spherical shape.
 10. The implantableprosthesis according to claim 1, wherein the body has a tubular shape.11. The implantable prosthesis according to claim 1, wherein the bodyhas a planar configuration at the proximal end and/or the distal end.12. The implantable prosthesis according to claim 1, further comprisinga first layer of biocompatible material located at the proximal end ofthe body and a second layer of biocompatible material located at thedistal end of the body, the first and second layers being oriented in adirection transverse to the core axis.
 13. The implantable prosthesisaccording to claim 12, wherein the first and second layers are formed ofabsorbable material.
 14. The implantable prosthesis according to claim12, wherein the first and second layers are formed of mesh fabric. 15.The implantable prosthesis according to claim 14, wherein the meshfabric is tissue infiltratable.
 16. The implantable prosthesis accordingto claim 1, wherein the body is formed of absorbable material.
 17. Theimplantable prosthesis according to claim 1, wherein the body is formedof mesh fabric.
 18. The implantable prosthesis according to claim 17,wherein the mesh fabric is tissue infiltratable.
 19. The implantableprosthesis according to claim 17, wherein each of the body segmentsincludes a sheet of mesh fabric.
 20. The implantable prosthesisaccording to claim 19, wherein the plurality of body segments areconnected together to form the plurality of chambers.
 21. Theimplantable prosthesis according to claim 1, wherein the plurality ofchambers are tissue infiltratable.
 22. The implantable prosthesisaccording to claim 1, wherein the body is configured to augment and/orreconstruct an anatomical shape of a human breast.